Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, U.K.
Unit for Population-Based Dermatology Research, St John's Institute of Dermatology, King's College London & Guy's and St Thomas' NHS Foundation Trust, London, U.K.
Br J Dermatol. 2019 Jun;180(6):1348-1351. doi: 10.1111/bjd.17624. Epub 2019 Mar 27.
Gordon et al. investigated the efficacy and safety of risankizumab [an anti-interleukin (IL)-23p19 biologic] compared with ustekinumab (anti-IL-12/23p40) and placebo in patients with moderate-to-severe chronic plaque psoriasis. This was a parallel-group controlled study up to 16 weeks with a planned switch of the placebo group to risankizumab at 16 weeks.
This study consisted of two replicate phase III, double-blinded randomized controlled trials (UltIMMa-1 and UltIMMa-2) conducted across 139 centres in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain and the U.S.A.
Patients with a minimum 6-month history of chronic plaque psoriasis were randomly assigned to receive either 150 mg risankizumab, 45 mg or 90 mg ustekinumab or placebo. Prior to this, each group was also stratified by weight (either more than or less than 100 kg) and previous exposure to tumour necrosis factor inhibitors. Those assigned to receive placebo were transitioned onto risankizumab at week 16. The study drugs were given at weeks 0, 4, 16, 28 and 40.
The severity of psoriasis was measured using the Psoriasis Area and Severity Index (PASI) and a static Physician's Global Assessment (sPGA). The authors additionally recorded the number of adverse events in each treatment arm, and a measure of quality of life.
The coprimary outcomes were the proportions of patients achieving ≥ 90% reduction in their baseline PASI (PASI 90) and an sPGA score of 0 or 1 (clear or almost clear) at week 16.
In total 506 patients were included in UltIMMa-1 and 491 patients in UltIMMa-2. In UltIMMa-1, PASI 90 by week 16 was achieved by 75·3% of patients receiving risankizumab, compared with 42·0% receiving ustekinumab and 4·9% receiving placebo (P < 0·001 vs. placebo and ustekinumab). sPGA of 0 or 1 by week 16 was achieved by 87·6% of patients receiving risankizumab, compared with 63·0% receiving ustekinumab and 7·8% receiving placebo (P < 0·001 vs. placebo and ustekinumab). The results for UltIMMa-2 are similar. The frequencies of adverse events in the risankizumab, ustekinumab and placebo groups were similar in both studies.
Gordon et al. conclude that risankizumab has a higher efficacy than placebo and ustekinumab in the treatment of moderate-to-severe chronic plaque psoriasis, and that the adverse-event profiles were similar across all treatment groups.
Gordon 等人研究了 risankizumab（一种抗白细胞介素（IL）-23p19 生物制剂）与 ustekinumab（抗 IL-12/23p40）和安慰剂在中重度慢性斑块型银屑病患者中的疗效和安全性。这是一项长达 16 周的平行组对照研究，计划在 16 周时将安慰剂组转换为 risankizumab。
这项研究由两项在澳大利亚、奥地利、比利时、加拿大、捷克共和国、法国、德国、日本、墨西哥、波兰、葡萄牙、韩国、西班牙和美国的 139 个中心进行的复制性 III 期双盲随机对照试验（UltIMMa-1 和 UltIMMa-2）组成。
有至少 6 个月慢性斑块型银屑病病史的患者被随机分配接受 150mg risankizumab、45mg 或 90mg ustekinumab 或安慰剂治疗。在此之前，每个组还根据体重（大于或小于 100kg）和以前是否接触过肿瘤坏死因子抑制剂进行分层。那些被分配接受安慰剂的人在第 16 周时转换为 risankizumab。研究药物在第 0、4、16、28 和 40 周时给予。
银屑病的严重程度使用银屑病面积和严重程度指数（PASI）和静态医师整体评估（sPGA）来衡量。作者还记录了每个治疗组的不良事件数量和生活质量的衡量标准。
主要结局是第 16 周时达到以下两个指标的患者比例：基线 PASI 降低≥90%（PASI 90）和 sPGA 评分 0 或 1（清除或几乎清除）。
在 UltIMMa-1 中共有 506 名患者入组，在 UltIMMa-2 中共有 491 名患者入组。在 UltIMMa-1 中，第 16 周时达到 PASI 90 的患者比例分别为接受 risankizumab 治疗的患者 75.3%，接受 ustekinumab 治疗的患者 42.0%，接受安慰剂治疗的患者 4.9%（与安慰剂和 ustekinumab 相比，均 P < 0.001）。第 16 周时达到 sPGA 0 或 1 的患者比例分别为接受 risankizumab 治疗的患者 87.6%，接受 ustekinumab 治疗的患者 63.0%，接受安慰剂治疗的患者 7.8%（与安慰剂和 ustekinumab 相比，均 P < 0.001）。UltIMMa-2 的结果类似。risankizumab、ustekinumab 和安慰剂组的不良事件发生率在两项研究中相似。
Gordon 等人的结论是，risankizumab 在治疗中重度慢性斑块型银屑病方面比安慰剂和 ustekinumab 更有效，并且所有治疗组的不良事件谱相似。
